Low-Dose Naltrexone Shows No Significant Pain Relief in Fibromyalgia Trial

A new study published in the journal of CNS Drugs showed that low-dose naltrexone (LDN) did not outperform placebo in reducing pain intensity or altering pressure pain thresholds in fibromyalgia patients. The FINAL trial's primary and exploratory analyses revealed no significant benefits of LDN in managing fibromyalgia-related pain.

Fibromyalgia has a complicated and multidimensional neurobiology, with theories of central sensitization. An opioid receptor antagonist called low-dose naltrexone (LDN) has become a novel treatment option for fibromyalgia patients, with the potential to lessen pain and enhance quality of life. Modification of central sensitization and improvement of pain inhibition are among the hypothesized mechanisms of LDN, which may be mediated via its anti-inflammatory qualities and effects on glial cell activity.

The aim of the secondary analyses was to investigate the possible effects of LDN in comparison to a placebo on 5 exploratory secondary outcomes in women with fibromyalgia following 12 weeks of treatment in the entire case population: pain tolerance, TSP, CPM, and upper and lower limb muscular endurance.

For 12 weeks, 99 fibromyalgia patients received either LDN or a placebo in the FINAL study, which was randomized and placebo-controlled. In the full case population (45 versus 47 individuals), we investigated the possible effects of LDN versus placebo on baseline changes in pain tolerance, temporal summation of pain, and conditioned pain modulation (CPM). A shoulder abduction test and the 30-second chair stand test were used to assess measures of muscle exhaustion.

With a larger enhancement after LDN therapy compared with placebo, the change in CPM was the only one of the five outcomes that demonstrated a meaningful between-group difference. According to within-group changes in CPM, the LDN group had a rise of 1.2 kPa, whereas the placebo group may have seen a drop of 0.8 kPa.

Overall, change in CPM was one of the five exploratory outcome measures that showed a significant difference between groups. A decline in CPM in the placebo group contributed to the between-group difference, and there was no correlation between the change in CPM and pain response, indicating that this finding is most likely erroneous.

Source:

Bruun, K. D., Christensen, R., Amris, K., Blichfeldt-Eckhardt, M. R., Bye-Møller, L., Henriksen, M., Alkjaer, T., Toft, P., Holsgaard-Larsen, A., & Vaegter, H. B. (2025). Effect of naltrexone on spinal and supraspinal pain mechanisms and functional capacity in women with fibromyalgia: Exploratory outcomes from the randomized placebo-controlled FINAL trial. CNS Drugs. https://doi.org/10.1007/s40263-025-01183-7